Aim To investigate the protective effect and mechanism of apigenin (APG) on cognitive function in vascular dementia (VD) rats. Methods The VD rat model was replicated by ligating bilateral common carotid arteries, and the sham group, model group, APG low-dose group, APG high-dose group, nimodipine (NMP) group were setted, with 30 rats in each group. The rats in APG low-dose group and high-dose group were administered intraperitoneally once a day at doses of 0,0 mg/kg APG respectively, the rats in the NMP group were administered intraperitoneally once a day at doses of 2 mg/kg NMP, the rats in the sham group and model group were given normal saline, the course of treatment was 28 days. The cognitive function was detected by Morris water maze test, the pathological characteristics and apoptosis of neurons in the CA1 region of the hippocampus were observed through HE staining and TUNEL staining, the ultrastructural changes of neurons was observed by electron microscopy. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in hippocampal were detected by spectrophotometric method. The mRNA and protein expression of nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by RT-PCR and Western blot. Results Compared with the model group, the cognitive function was significantly improved of rats in the APG high-dose group and NMP group; the number of neurons of hippocampus CA1 area, morphological and structural pathological changes, ultra-micromorphological changes and apoptosis were significantly improved, the pathological grade and apoptosis index (AI) were reduced; the content of MDA in the hippocampus was decreased, and the activity of SOD, GSH-Px were increased; the mRNA and protein expression of Nrf2, HO-1 were increased. The APG high-dose group had better effects on all indicators than those of NMP group. ConclusionAPG can significantly improve the cognitive function of VD rats, which may be related to the activating Nrf2/HO-1 pathway by APG, inhibiting oxidative stress and reducing brain hippocampus damage.